TBK1
Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents. Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRFs leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNA and IFNB. In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli. Plays a key role in IRF3 activation: acts by first phosphorylating innate adapter proteins MAVS, TMEM173/STING and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1. Phosphorylated IRF3 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce expression of interferons. Thus, several scaffolding molecules including FADD, TRADD, MAVS, AZI2, TANK or TBKBP1/SINTBAD can be recruited to the TBK1-containing-complexes. Under particular conditions, functions as a NF-kappa-B effector by phosphorylating NF-kappa-B inhibitor alpha/NFKBIA, IKBKB or RELA to translocate NF-Kappa-B to the nucleus. Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy. Phosphorylates SMCR8 component of the C9orf72-SMCR8 complex, promoting autophagosome maturation. Phosphorylates and activates AKT1. Seems to play a role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Attenuates retroviral budding by phosphorylating the endosomal sorting complex required for transport-I (ESCRT-I) subunit VPS37C. Phosphorylates Borna disease virus (BDV) P protein. Plays an essential role in the TLR3- and IFN-dependent control of herpes virus HSV-1 and HSV-2 infections in the central nervous system. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily. Ubiquitous with higher expression in testis. Expressed in the ganglion cells, nerve fiber layer and microvasculature of the retina. Note: This description may include information from UniProtKB.
Protein type: EC 2.7.11.1; IKK family; Kinase, protein; Other group; Protein kinase, Other; Protein kinase, Ser/Thr (non-receptor)
Molecular Function: ATP binding; identical protein binding; nucleic acid binding; phosphoprotein binding; protein binding; protein kinase activity; protein phosphatase binding; protein serine kinase activity; protein serine/threonine kinase activity
Biological Process: activation of innate immune response; antiviral innate immune response; cytosolic pattern recognition receptor signaling pathway; defense response to Gram-positive bacterium; defense response to virus; dendritic cell proliferation; I-kappaB kinase/NF-kappaB signaling; inflammatory response; innate immune response; negative regulation of gene expression; peptidyl-serine phosphorylation; peptidyl-threonine phosphorylation; positive regulation of autophagy; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of interferon-alpha production; positive regulation of interferon-beta production; positive regulation of macroautophagy; positive regulation of peptidyl-serine phosphorylation; positive regulation of transcription by RNA polymerase II; positive regulation of type I interferon production; positive regulation of type I interferon-mediated signaling pathway; positive regulation of xenophagy; protein phosphorylation; regulation of neuron death; regulation of tumor necrosis factor-mediated signaling pathway; regulation of type I interferon production; response to virus; type I interferon-mediated signaling pathway
